RESUMEN
We examined the effects of diets based on a low isoflavone or a high isoflavone soy protein isolates in normal, growth-hormone receptor knockout and Ames dwarf, and Prop 1 (df) mice that are hypoinsulinemic, insulin-sensitive, and exceptionally long-lived, as well as in growth hormone transgenic mice that are hyperinsulinemic, insulin-resistant, dyslipidemic, and short-lived. Soybean diets tended to normalize plasma cholesterol levels in dwarf and transgenic mice, while low isoflavone diet reduced plasma triglycerides in most of the examined genotypes. The effects of low isoflavone and high isoflavone diets on the levels of free and esterified cholesterol in the liver were strongly genotype-dependent. Fasting blood glucose levels were reduced and glucose tolerance improved by both low isoflavone and high isoflavone diets in growth hormone-transgenic mice and in their normal siblings. Glucose tolerance was also improved by high-isoflavone diet in growth hormone receptor knockout mice. Lifespan was increased by low isoflavone diet in normal mice from two of the examined stocks. High isoflavone diet increased lifespan in normal animals from one line, but reduced lifespan of normal mice from a different line. We conclude that dietary soy protein intake can improve plasma and hepatic lipid profiles, reduce fasting glucose, enhance capacity for glucose tolerance, and prolong life, but all of these effects are strongly genotype-dependent.
Asunto(s)
Dieta , Glucosa/fisiología , Glycine max , Metabolismo de los Lípidos , Hígado/metabolismo , Longevidad , Animales , Glucemia/metabolismo , Peso Corporal , Caseínas/administración & dosificación , Colesterol/metabolismo , Enanismo/genética , Enanismo/metabolismo , Enanismo/fisiopatología , Femenino , Prueba de Tolerancia a la Glucosa , Hormona de Crecimiento Humana/genética , Humanos , Isoflavonas/administración & dosificación , Lípidos/sangre , Hígado/anatomía & histología , Masculino , Ratones , Ratones Endogámicos , Ratones Noqueados , Ratones Transgénicos , Tamaño de los Órganos , Concentración Osmolar , Receptores de Somatotropina/deficiencia , Proteínas de Soja/administración & dosificación , Triglicéridos/metabolismoRESUMEN
Soy protein diets lower plasma cholesterol in hyperlipoproteinemic human subjects, as well as in animal models. We fed 7-wk-old male obese (fa/fa) and lean Zucker rats a modified AIN-76 diet (20 g protein/kg diet) containing casein (C), low isoflavone soy protein (38 mg isoflavones/kg diet; LI), or high isoflavone soy protein (578 mg isoflavones/kg diet; HI) for 70 d. In obese rats, plasma total cholesterol was 21 and 29% lower in the LI and HI groups, respectively, than in the C group (P: = 0.004). Liver weight and liver triglyceride and cholesteryl ester concentrations were 27, 33 and 46% lower, respectively, in the LI group than in the C group (P: < 0.003). These liver measurements were 23, 24 and 57% lower, respectively, in the HI group than in the LI group (P: < 0.05). In a complementary study, 5-wk-old male Sprague-Dawley rats were fed the same C, LI and HI diets for 42 d. Thrombin-mediated platelet serotonin release in vitro was 13% lower in the HI group than in the C group (P: = 0.003). In a third study, 7-wk-old male Sprague-Dawley rats were fed either a modified AIN-76 control diet or a high fat casein-based atherogenic diet (140 g fat, 12 g cholesterol, and 2 g cholic acid/kg diet) with or without a soy isoflavones extract (983 mg isoflavones/kg diet) for 63 d. Addition of the isoflavones extract to the atherogenic diet lowered the liver triglyceride concentration by 33% relative to the atherogenic diet without isoflavones (P: = 0.0001). Our studies suggest that the hypocholesterolemic mechanism of dietary soy protein involves a cooperative interaction between the protein and isoflavone-enriched fraction that lowers hepatic lipid concentrations. We speculate that modulation of liver and plasma lipid homeostasis can also lower blood platelet sensitivity.
Asunto(s)
Plaquetas/efectos de los fármacos , Colesterol/sangre , Dieta Aterogénica , Isoflavonas/farmacología , Metabolismo de los Lípidos , Hígado/efectos de los fármacos , Proteínas de Soja/farmacología , Análisis de Varianza , Animales , Peso Corporal/efectos de los fármacos , Interacciones Farmacológicas , Isoflavonas/administración & dosificación , Lípidos/sangre , Hígado/metabolismo , Masculino , Tamaño de los Órganos/efectos de los fármacos , Ratas , Ratas Sprague-Dawley , Ratas Zucker , Proteínas de Soja/administración & dosificaciónRESUMEN
2-Hydroxypropyl-beta-cyclodextrin (cyclodextrin), cyclodextrin-solubilized oleate, and cyclodextrin-solubilized cholesterol were used to modulate proteolysis and secretion of newly-synthesized apolipoprotein B-100 (apoB) in HepG2 cells. Following cyclodextrin and lipid treatments, cells were pulse-labeled with [3H] leucine, and quantitative immunoprecipitation was used to measure apoB synthesis, apoB secreted into the medium, and the cellular content of undegraded apoB that was not secreted. Three-hour treatment with cyclodextrin-solubilized oleate (0.2 mM) increased secreted apoB from 4% (control cells) to 32% and cellular undegraded apoB from 15% (control cells to 64% of apoB synthesized, which is consistent with earlier studies using bovine serum albumin to complex exogenous oleate. Prolonged daily (4 d or more) administration of 0.5% (3.5 mM) cyclodextrin with medium containing 10% fetal bovine serum increased the secretion of nascent apoB from 5-10% (control) to 17-28% and cellular undegraded apoB from 15-20% (control) to 25-31% of apoB synthesized, respectively. Subsequent administration of cyclodextrin solubilized cholesterol (10-40 micrograms) for only 3 h reversed the cyclodextrin-mediated increase in apoB secretion. The application of 0.5% cyclodextrin to HepG2 cells can rapidly (within minutes) stimulate cholesterol efflux, and transiently (over a 1-2 d period) increase cholesterol synthesis. In the current studies, the cyclodextrin-mediated increase in cholesterol synthesis was not concurrent with the increase in apoB secretion. However, prolonged (15 d) administration of cyclodextrin was shown to increase the cellular free cholesterol concentration by 25-41%, reduce the cellular triglyceride concentration by 59%, and increase apoB secretion 3- to 4-fold, without affecting the cellular cholesteryl ester concentration. In comparison, 14-d treatment with cyclodextrin-solubilized cholesterol (20 micrograms/mL) followed by 1-d equilibration without cholesterol was shown to increase the cellular free cholesterol and cholesteryl ester concentrations by 76% and 10-fold, respectively, although apoB secretion was not affected. It is hypothesized that chronic daily administration of 0.5% cyclodextrin increased the cellular cholesterol concentration and flux in discrete putative regulatory compartments, which "shielded" nascent apoB from rapid proteolysis and facilitated apoB secretion. In conclusion, cyclodextrin was used independently and in combination with cholesterol or oleate to modulate apoB proteolysis and secretion. We speculate that subcellular changes in cholesterol concentration and flux may modulate apoB production in HepG2 cells.
Asunto(s)
Apolipoproteínas B/metabolismo , Colesterol/metabolismo , Ciclodextrinas/farmacología , Ácido Oléico/metabolismo , beta-Ciclodextrinas , 2-Hidroxipropil-beta-Ciclodextrina , Ácido Acético/metabolismo , Apolipoproteína B-100 , Apolipoproteínas B/biosíntesis , Electroforesis en Gel de Poliacrilamida , Endopeptidasas/metabolismo , Humanos , Neoplasias Hepáticas , Ácido Oléico/farmacología , Proteínas/metabolismo , Solubilidad , Células Tumorales CultivadasRESUMEN
Silicon dioxide, commonly referred to as silica, is present in plant cell walls and interstitial spaces, and is often found as a component of dietary fibers that have exhibited hypocholesterolemic activity in animals. The primary objective of this study was to determine the cholesterolemic effects of two different morphological forms of silicon in the diet of cholesterol-fed rats. Male Wistar rats were provided diets containing 1 g cholesterol/100 g diet, and 0.65 g Si/100 g diet as either a sodium salt (silicate group) or silicon dioxide, a synthetic silica polymer (silica group). Cellulose was used as a control (control group). The in vitro bile acid binding capacity of the SiO2 was also measured. After 44 d of diet administration, animals were deprived of food for 24 h and then killed. Plasma total, VLDL, and LDL cholesterol concentrations were 18%, 29%, and 26% lower, respectively, in the silica group than in the control group. However, liver cholesterol concentrations were not different among dietary treatments. During the initial 15 d of the study, average daily total fecal bile acids were 38% higher in the silica group than in the control group, but fecal bile acid outputs were not different for the remainder of the experiment. The silica polymer used in the feeding trial was found to adsorb 5 times more cholate than chenodeoxycholate, at pH 7.5 in vitro. In vivo, the potential for silica to enhance fecal cholic acid excretion, relative to chenodeoxycholic acid during the initial stage of the study, may have contributed to the hypocholesterolemic response to the silica diet.(ABSTRACT TRUNCATED AT 250 WORDS)